Phosphodiester photo-tethers for the (multi-)cyclic conformational caging of oligonucleotides.

The ability to address the function of oligonucleotides with light is highly desirable since they are often used experimentally in the regulation of biological processes that need to be controlled in time, space and activation level. Here we present an extension of our initial approach of using photo-tethers that force single strands of nucleic acids into a circle, thus making them unable to form a duplex with a complementary DNA- or RNA-strand. Due to the persistence length a single strand can form a circle of, for example, 30 nucleotides, but a duplex cannot. We show that these new photo-tethers can also be easily installed on the phosphodiester backbone. This simplifies the approach considerably and leads to temporarily inhibited oligonucleotides that can only form a duplex after linearization by photoactivation.